Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

Janet Kairu, Mercer University College of Pharmacy

According to the National Comprehensive Cancer Network (NCCN), renal cell carcinoma (RCC) accounts for 2%–3% of all adult malignancies, with a media age at diagnosis of 65 years.  The NCCN suggests that smoking and obesity are among the highest risk factors for RCC development.  They mention that several hereditary types of RCC also exist, with von Hippel-Lindau disease (VHL) being the most common, caused by a mutation in the VHL gene predisposing to clear cell carcinoma. [1]

The American Society for Medical Oncology mention there has been considerable progress in the treatment of renal-cell carcinoma since 2005, with five vascular endothelial growth factor  (VEGF)-pathway inhibitors (sorafenib, sunitinib, bevacizumab, pazopanib, and axitinib) and two mammalian target of Rapamycin (mTOR) inhibitors (everolimus and temsirolimus) showing benefit in pivotal phase 3 trials, and have led to regulatory approval.[2]

Table 1.

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma [3]
Design Randomized, open-label, phase 3 study trial; N = 821
Objective To compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment
Study Groups Nivolumab three mg per kilogram of body weight intravenously every two weeks or a 10-mg everolimus tablet orally once daily
Methods Patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive nivolumab every two weeks or everolimus once daily.
Duration October 2012 to March 2014
Primary Outcome Measure Overall survival

(n = 410)


(n= 411)


(n = 821)

Median age (years) 62 (23-88) 62 (18-86) 62 (18-88)
Male 315 (77) 304 (74) 619 (75)
Female 95 (23) 107 (26) 202 (25)
Favorable MSKCC risk group, no. (%)

(Memorial Sloan Kettering Cancer Center)

145 (35) 148 (36) 293 (36)
Intermediate MSKCC, no. (%) 201 (49) 203 (49) 404 (49)
Poor MSKCC, no. (%) 64 (16) 60 (15) 124 (15)
Previous Therapy:
Sunitinib 246 (60) 242 (59) 488 (59)
Pazopanib 119 (29) 131 (32) 250 (30)
Axitinib 51 (12) 50 (12) 101 (12)
Results No. of Patients Median Overall Survival (95% CI) No. of Death
Nivolumab 410 25.0 (21.8 – NE) 183
Everolimus 411 19.6 (17.6 – 23.1) 215
Hazard ratio, 0.73 (98.5% CI, 0.57–0.93) p = 0.002

NE; not estimable

Adverse Events Common Adverse Events: Fatigue, nausea, pruritus
Serious Adverse Events: Not reported
Percentage that Discontinued due to Adverse Events: Occurred in 31 of the 406 patients (8%) treated with nivolumab and in 52 of the 397 patients (13%) treated with everolimus
Study Author Conclusions Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade three or four adverse events occurred with nivolumab than with everolimus.

This study also showed a higher number of objective responses with nivolumab than with everolimus, many of which were durable.  The median progression-free survival was similar in the two treatment groups and was consistent with that reported in an uncontrolled study involving patients who had previously received antiangiogenic therapy.  Moreover, the results of a comparison of progression-free survival between the nivolumab group and the everolimus group suggest that progression-free survival was not a surrogate for overall survival in this study.

The trial was stopped early after meeting the primary endpoint, and eligible patients in the everolimus cohort were allowed to cross over and receive nivolumab in an open-label extension of the study.


  1. Motzer RJ, Agarwal N, Beard C, et al. NCCN clinical practice guidelines in oncology: kidney cancer. J Natl Compr Canc Netw. 2009;7(6):618-30.
  1. Bellmunt J, Puente J, Garcia de Muro J, Lainez N, Rodríguez C, Duran I. SEOM clinical guidelines for the treatment of renal cell carcinoma. Clinical & Translational Oncology. 2014;16(12):1043-1050
  1. Motzer RJ, Escudier B, Mcdermott DF, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373(19):1803-13.

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